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Neutralizing monoclonal antibody against Dickkopf2 impairs lung cancer progression via activating NK cells

Tianli Shen1,2, Zhengxi Chen2,3, Ju Qiao4

  • 11Department of General Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi China.

Cell Death Discovery
|August 3, 2019
PubMed

Insights

Targeting Dickkopf-related protein 2 (DKK2) with an antibody shows promise for treating non-small cell lung cancer (NSCLC) with Adenomatous polyposis coli (APC) mutations. This approach modulates the tumor immune microenvironment, offering a new therapeutic strategy.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Adenomatous polyposis coli (APC) and KRAS mutations are common in non-small cell lung cancer (NSCLC).
  • Inactivating APC mutations in colorectal cancer are well-studied, but their therapeutic implications in NSCLC are unclear.
  • Dickkopf-related protein 2 (DKK2), a Wnt antagonist, was previously shown to be a target for APC-mutated colorectal tumors.

Purpose of the Study:

  • To investigate the efficacy of anti-DKK2 antibody therapy in NSCLC with APC mutations.
  • To determine if targeting DKK2 is a viable strategy for APC-mutated lung cancers.

Main Methods:

  • Analysis of Dkk2 expression in APC-mutated lung cancers.
  • In vivo studies using lung cancer mouse models treated with anti-DKK2 antibody.
  • Evaluation of the antibody's effect on tumor growth and the tumor immune microenvironment.

Main Results:

  • Significant upregulation of Dkk2 expression was observed in APC-mutated lung cancers.
  • Administration of anti-DKK2 antibody inhibited tumor growth in lung cancer mouse models.
  • The antibody treatment modulated the tumor immune microenvironment.

Conclusions:

  • Anti-DKK2 antibody therapy is a potential treatment strategy for NSCLC patients with APC mutations.
  • Targeting DKK2 offers a promising therapeutic avenue for a broader range of APC-mutated cancers, including lung cancer.
Keywords:
Lung cancerTumour immunology

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